The goal of this research program is a better understanding of the mechanisms of cardiovascular disease. The program includes a variety of projects ranging from molecular structure to human disease. This broad spectrum of investigations may be related to five general themes: circulatory control mechanisms, vascular integrity and disease, myocardial mechanical performance, electrical stability of the heart, and the use of biophysical models to augment the effectiveness of the biological research. Control of the circulation is studied relative to cardiac operative procedures, the physiology of coronary flow, the biophysics of pulsatile flow in tubes, and neural influence on the heart and vessels. Vascular integrity is investigated by research on the biochemical composition of collagen, the molecular basis for calcification of elastin, detailed biochemical aspects of heparin and other mucopolysaccharides, viral vascular pathology and the immunological basis of vascular disease. Myocardial contraction is investigated in experimental animals with the heart intact and by special preparation of strips of myocardium, while ventricular function is studied in man under a variety of abnormal states. Electrical stability of the heart is the theme of work on the basis of impulse formation and conduction in man and experimental animals, and includes research on special electrical properties of cells as well as the determinants of arrhythmias and conduction disturbances in man. All these separate projects are greatly facilitated by the availability and frequent use of mathematical and biophysical models, both to improve analysis of biological data and to plan future research in vivo. Over a decade of collaborative experience by members of this program forms a basis for sustained future productivity from a search for improved diagnosis and treatment of human cardiovascular disease.